Expression of DNA repair genes in some Black women may be linked to higher breast cancer mortality rates
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Black women in the US have a higher mortality rate from breast cancer than white women. This may be in part due to differences in how a person’s environment affects the expression of genes involved in DNA repair.
“These differences aren’t about mutations that are in you from the moment you’re born, but are instead about how cells adapt to your environment,” says Svasti Haricharan at the Sanford Burnham Prebys Medical Discovery Institute in California. There is no genetic basis to race, she says, but our environments and our lifestyles affect our biology.
Haricharan and her colleagues analysed breast tissue data from 847 women, including 144 Black women. This shows the lack of tumour samples from Black women in general in US data sets, she says.
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Most of the women had been diagnosed with a common type of breast cancer, while some samples used as a control were from healthy breast tissue in women without cancer.
“Oestrogen receptor positive cancer is the most common type of breast cancer diagnosed in the world,” says Haricharan. “Based on estimates, it accounts for about 60 to 80 per cent of breast cancer.”
Previous studies have found that Black women are 42 per cent more likely to die from this type of cancer than white women. Structural racism, socioeconomics and lifestyle all play a role in this disparity, says Haricharan, but it is also important to study differences in molecular biology. “By better understanding this biology, we can tailor treatments for people from different demographics,” she says.
The researchers focused their efforts on genes that drive DNA repair mechanisms, which have been shown in previous studies to affect how well a person with breast cancer responds to a treatment called endocrine therapy. This therapy slows tumour growth by stopping a person from producing growth-stimulating hormones.
Genes involved in the repair of DNA damage also affect how hormones alter cell growth as they play a role in how cells divide and multiply. The researchers found eight DNA damage repair genes that were expressed differently in a subset of Black women than in white women and other Black women.
The team found these differences in between 6 and 15 per cent of Black women in their sample. “I don’t want to put a specific number on it because of the small sample size,” says Haricharan. The team did not look at whether this altered gene expression explicitly made endocrine therapy less effective but speculate that such a gene expression would lead to treatment resistance.
“We saw these differences exclusively in Black women,” says Haricharan. “[This altered gene expression is] almost undetectable in white women.” This difference in gene expression is due to the differences in peoples’ environments. While the genes we possess are due to our ancestry, the way they are expressed is affected by circumstances, such as how much stress people face and the type of diet they eat.
Haricharan believes that overlooking these differences when treating people can have real consequences. “Precision medicine today is based on white people,” she says. “And I think people who come from other backgrounds, other races, other ethnicities – who might have different molecular signals – we’re not taking that into account.”
For example, the team found a link between an altered expression of the eight DNA repair genes and higher levels of cyclin-dependent kinases (CDKs) in a person’s cells. These molecules cause cancer cells to multiply faster and are targeted in cancer therapy by inhibitor drugs.
Haricharan says doctors only prescribe CDK inhibitors after seeing that endocrine therapy is having an effect, but giving CDK inhibitors earlier may work better for Black women who have this altered gene expression.
“Although the findings are interesting, it certainly isn’t enough to explain the entirety of the difference we see,” says Navita Somaiah at the Institute of Cancer Research in the UK. “The patient numbers are too small, and it’ll need larger data sets to validate the findings.”
“However, along with other papers published on this topic, it highlights the need to consider molecular differences linked to ethnicity when developing future therapies,” she says.
The lack of cancer tissue samples from Black people and those in other ethnic minority groups is holding back research into effective treatment, says Haricharan. “People of colour have a historical mistrust of the medical establishment and so are less likely to provide medical samples, but it’s important we try to rebuild this trust.”
Journal reference: Therapeutic Advances in Medical Oncology, DOI: 10.1177/17588359221075458
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